Rare syndromic craniosynostosis or isolated multisuture synostosis

Gene: SMO

Green List (high evidence)

Green for L412F in affected tissue (mosaic). Associated with unicoronal CSS. Green? - recurrent somatic mosaic variant L412F in affected tissue. Need deep seq and affected tissue - better done by different method? ; Review on behalf of Tracy Lester/Andrew Wilkie

Created: 5 Mar 2019, 11:33 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Curry-Jones syndrome, somatic mosaic, 601707

Publications

• 27236920

Mode of pathogenicity
Other - please provide details in the comments

I don't know

This gene was part of an initial gene list collated by Tracy Lester, Oxford Medical Genetics Laboratories, Oxford University Hospitals NHS Foundation Trust, February 2019 on behalf of the GMS Musculoskeletal Specialist Group; Gene symbol submitted: SMO; Suggested initial gene rating: green

Created: 5 Mar 2019, 11:21 a.m.

Comment on mode of inheritance: Changed MOI from 'Other' in order to capture variants within this gene in our current tiering pipeline.

Created: 5 Nov 2018, 9:05 a.m.

Note that the current pipeline has the potential for not detecting mosaic conditions, which is dependant on the mutational load and sample tested.

Created: 30 Aug 2017, 10:22 a.m.

Comment on list classification: changed status from Amber to Green due clinical review and evidence in the literature

Created: 30 Aug 2017, 10:16 a.m.

added tags mosaicism and somatic

Created: 16 Aug 2017, 10:10 a.m.

Comment on list classification: Changed from Grey to Amber- need to check with clinical team to consider making Green

Created: 15 Aug 2017, 12:40 p.m.

Comment on phenotypes: added MIM id

Created: 15 Aug 2017, 12:32 p.m.

Green List (high evidence)

Identical mosaic mutation (c.1234C>T; p.Leu412Phe) identified in 8 unrelated cases of Curry Jones syndrome. Functional studies confirm this is gain-of-function, likely lethal as germline mutation. Associated phenotypes are patchy skin lesions, polysyndactyly, diverse cerebral malformations, unicoronal craniosynostosis, iris colobomas, microphthalmia, and intestinal malrotation with myofibromas or hamartomas.Cerebellar medulloblastoma has been described in a single affected individual.

Created: 11 Nov 2016, 12:41 p.m.

Mode of inheritance
Other

Phenotypes
Curry-Jones syndrome

Publications

• 27236920

Mode of pathogenicity
Other